Cerebral Cortex Communications

In preschool years, children take important steps in grammar acquisition, which are essential to learning their native language. A central aspect is the acquisition of the morpho-syntactic rule system, which forms an intersection between words and sentences. In adults, rule-based linguistic processes are supported by the dorsal fiber pathway to BA44, the arcuate fascicle. This pathway matures relatively late in development, raising the question of whether it already supports grammar processes in the early preschool years, or whether early grammar acquisition is supported by different, earlier-maturing fiber pathways. In two independent samples of 3- to 5-year-old children (N = 90 and N = 30), we examined the association between the maturation of fiber pathways of the language network and childrens noun plural assignment as an index of their morpho-syntactic abilities. This revealed consistent differences between 3-year-olds and 4- to 5-year-olds. The 4- and 5-year-olds, but not 3-year-olds, showed a relation of morpho-syntax with both the dorsal pathway to BA44, supporting syntactic processes, and the dorsal pathway to BA6, supporting phonological processes in adults. Our results suggest that, in contrast to adults, preschool-aged children rely on both dorsal fiber pathways for morpho-syntax. This difference might point to different processing strategies reflecting the transition from phonology-based statistical learning to rule-based learning in grammar acquisition.

IntroductionThe motor system shows a pronounced development throughout childhood and adolescence. The analysis of the contingent negative variation (CNV) provides valuable insights into various cognitive and motor processes, underlying cortical sources, and their development across the lifespan. MethodsWe investigated the maturation of motor preparation, pre-activation and post-processing in children and adolescents aged 5- to 16- years. EEG Data of 46 healthy right-handed subjects were recorded, using a 64-electrode high density sensor array. Subjects performed a CNV task with a directional warning cue. To assess age related developmental differences of cortical activation, analyses of event-related potentials (ERPs), mu-rhythm (de)synchronization and source analysis were applied. ResultsChildren showed increased reaction times and committed more errors than adolescent subjects. Motor preparation and post-processing were characterized by a developmental increase of cortical activity related to the supplementary motor area (SMA). Young children showed a pronounced sensory post processing during orienting response (early CNV) that decreased with age. In contrast to previous research in young adults, adolescent subjects showed no contralateral activation of motor areas during motor preparation (late CNV) yet. Furthermore, there was an observed decline in motor post processing with maturation. ConclusionThe results indicate a prolonged maturation of cortical scalp areas associated with motor control up into late adolescence or early adulthood. With age, the activation of mid-frontocentral regions associated with the SMA becomes more pronounced during motor planning and response evaluation. Qualitatively distinct cortical activation patterns of young subjects suggest immature supplementary-, pre- and primary motor areas and might be a primary cause for age-related increasing efficiency of motor action control.

BackgroundThe piriform cortex has been implicated in the initiation, spread and termination of epileptic seizures. This understanding has extended to surgical management of epilepsy, where it has been shown that resection or ablation of the piriform cortex can result in better outcomes. How and why the piriform cortex may play such a crucial role in seizure networks is not well understood. To answer these questions, we investigated the functional and structural connectivity of the piriform cortex in both healthy controls and temporal lobe epilepsy (TLE) patients. MethodsWe studied a retrospective cohort of 55 drug-resistant unilateral TLE patients and 26 healthy controls who received structural and functional neuroimaging. Using seed-to-voxel connectivity we compared the normative whole-brain connectivity of the piriform to that of the hippocampus, a region commonly involved in epilepsy, to understand the differential contribution of the piriform to the epileptogenic network. We subsequently measured the inter-piriform coupling (IPC) to quantify similarities in the inter-hemispheric cortical functional connectivity profile between the two piriform cortices. We related differences in IPC in TLE back to aberrations in normative piriform connectivity, whole brain functional properties, and structural connectivity. ResultsWe find that relative to the hippocampus, the piriform is functionally connected to the anterior insula and the rest of the salience ventral attention network (SAN). We also find that low IPC is a sensitive metric of poor surgical outcome (sensitivity: 85.71%, 95% CI: [19.12%, 99.64%]); and differences in IPC within TLE were related to disconnectivity and hyperconnectivity to the anterior insula and the SAN. More globally, we find that low IPC is associated with whole-brain functional and structural segregation, marked by decreased functional small-worldness and fractional anisotropy. ConclusionsOur study presents novel insights into the functional and structural neural network alterations associated with this structure, laying the foundation for future work to carefully consider its connectivity during the presurgical management of epilepsy.

The relationship between motor intention and initiation of voluntary movement remains a fundamental topic in neuroscience, originating from the B. Libet seminal framework introduced in 1983. Libets paradigm significantly influenced discussions on intentionality, motor control, and free will. However, methodological critiques continue to challenge its interpretations, specifically the accuracy and validity of the urge to move phenomenon. One understudied factor in this debate is the potential influence of interoceptive signals--particularly cardiac activity--in shaping the experience of motor intention and movement initiation. In our study, we addressed this gap by examining whether cardiac signals modulate participants experience of the urge to move, using behavioural and electrophysiological measures in 34 healthy human participants performing Libets task. Crucially, when participants were asked to report the perceived urge to move, their button press timings were predominantly aligned with the diastolic phase of the cardiac cycle, indicating cardiac modulation of motor intention perception. However, analysing heart evoked potential (HEP) amplitudes as a measure of cardiac input perception, we observed no differences in HEP amplitudes associated with changes in introspective demands during the task in both source and sensor spaces. Our results suggest that implicit perception of cardiac signals biases subjective experience of voluntary action initiation, independent from cortical interoceptive markers. These findings have implications for models of motor preparation, intentionality and the bodily basis of voluntary action, challenging conventional interpretations of motor intention and informing debates on volition and interoception. Significance StatementOur study provides evidence that implicit perception of cardiac signals influences the subjective experience of motor intention--the urge to move in Libets experiment. We demonstrate, for the first time, that when reporting urge to move, participants tended to initiate voluntary movements during the diastolic phase of the cardiac cycle. These findings challenge traditional views on factors affecting motor initiation, suggesting relevance of interoceptive processing. By highlighting the role of cardiac input in experiencing motor intention, our findings impact existing debates on volition, agency and free will, further underscoring the importance of integrating bodily signals into these theoretical frameworks.

BackgroundAmerican tackle football is associated with high rates of concussion, leading to neurophysiological disturbances and debilitating clinical symptoms. Previous investigations of the neurophysiological effects of concussion have largely ignored aperiodic neurophysiological activity, which is a marker of cortical excitability. PurposeWe examined whether concussion during a season of high school football is related to changes in aperiodic and periodic neurophysiological activity and whether any such changes are associated with clinical outcomes. Materials and MethodsPre- and post-season resting-state magnetoencephalography (MEG) data were collected from 91 high school football players over as many as four seasons of play, for a total of 278 data collections. During these seasons of football play, a cohort of 10 individuals were diagnosed with concussion. MEG data were source-imaged, frequency-transformed and parameterized, and linear mixed models were used to examine effects of concussion on pre-to-post-season changes in neurophysiological activity. Scores on the Post-Concussive Symptom Inventory were correlated with pre-to-post-season neurophysiological changes to determine their clinical relevance. ResultsConcussion was associated with increased aperiodic exponents in superior frontal cortices, indicating a relative reduction in cortical excitability. This slowing of aperiodic neurophysiology mediated concussion effects on raw delta and gamma power and was associated with worse cognitive concerns across participants. Pre-to-post-season changes in aperiodic-corrected alpha and theta rhythmic activity were also decreased in posterior cortices in concussed players. ConclusionThese findings indicate that concussion alters both the excitability and rhythmic signaling of the cortex, with differing spatial topographies and implications for clinical symptoms. Key ResultsO_LIConcussion reduces cortical excitability in superior frontal cortices. C_LIO_LIThis reduction accounts for canonical effects of concussion on delta and gamma power. C_LIO_LIConcussion-related changes in cortical excitability are associated with increased cognitive symptom severity. C_LI

Successful human hand and arm movements are typically carried out by combining visual, motoric, and proprioceptive information in planning, initiation, prediction, and control. The superior parietal lobule (SPL) has been argued to play a key role in integrating visual and motoric information particularly during grasping of objects and other such tasks which prioritise visual information. However, sign language production also engages SPL even though fluent signers do not visually track their hands or fixate on target locations. Does sign language production simply rely on the motoric/ proprioceptive processes engaged in visually guided action, or do the unique characteristics of signed languages change these processes? Fifteen fluent British Sign Language users named pictures while we administered transcranial magnetic stimulation (TMS) to left SPL, a control site, or no TMS. TMS to SPL had very specific effects: an increased rate of (sign-based) phonological substitution errors for complex two-handed signs (those requiring hand contact), but TMS did not slow or otherwise impair performance. Thus, TMS decreased the likelihood of detecting or correcting phonological errors during otherwise successful bimanual coordination, but it did not noticeably alter fine movement control. These findings confirm that for fluent signers SPL has adapted to monitor motor plans for discrete hand configurations retrieved from memory as well as more fine-grained aspects of visually guided actions.

Timing is everything, but our understanding of the neural mechanisms of timing remains limited, particularly for timing of sequences. Temporal sequences can be represented relative to a recurrent beat (beat-based or relative timing), or as a series of absolute durations (non-beat-based or absolute timing). Neuroimaging work suggests involvement of the basal ganglia, supplementary motor area (SMA), the premotor cortices, and the cerebellum in both beat- and non-beat-based timing. Here we examined how beat-based timing and non-beat-based sequence timing were affected by modulating excitability of the supplementary motor area, the right cerebellum, and the bilateral dorsal premotor cortices, using transcranial direct current stimulation (tDCS). Participants were subjected to a sham stimulation session, followed an active stimulation session where anodal or cathodal 2mA tDCS was applied to the SMA, right premotor cortex, left premotor cortex, or the cerebellum. During both sessions, participants discriminated changes in rhythms which differentially engage beat-based or non-beat-based timing. Rhythm discrimination performance was improved by increasing SMA excitability, and impaired by decreasing SMA excitability. This polarity-dependent effect on rhythm discrimination was absent for cerebellar or premotor cortex stimulation, suggesting a crucial role of the SMA and/or its functionally connected networks in rhythmic timing mechanisms.

In recent years, research on voice processing in the human brain--particularly the study of temporal voice areas (TVA)--was dedicated almost exclusively to conspecific vocalizations. To characterize commonalities and differences regarding primate vocalization representations in the human brain, the inclusion of closely related nonhuman primates--namely chimpanzees and bonobos--is needed. We hypothesized that neural commonalities would depend on both phylogenetic and acoustic proximities, with chimpanzees ranking closest to Homo. Presenting human participants (N=23) with the vocalizations of four primate species (rhesus macaques, chimpanzees, bonobos and humans) and regressing-out relevant acoustic parameters using three distinct analyses, we observed within-TVA, sample-specific, bilateral anterior superior temporal gyrus activity for chimpanzee vocalizations compared to: all other species; nonhuman primates; human vocalizations. Within-TVA activity was also observed for macaque vocalizations. Our results provide evidence for subregions of the TVA that respond principally--but not exclusively--to phylogenetically and acoustically close nonhuman primate vocalizations, namely those of chimpanzees.

Extensive neuroimaging literature suggests that understanding others thoughts and emotions engages a wide network encompassing parietal, temporal and medial frontal brain areas. However, the causal role played by these regions in social inferential abilities is still unclear. Moreover very little is known about ToM deficits in brain tumours and whether potential anatomical substrates are comparable to those identified in fMRI literature. This study evaluated the performance of 105 tumour patients, before and immediately after brain surgery, on a cartoon-based non-verbal task evaluating Cognitive (Intention Attribution) and Affective (Emotion Attribution) ToM, as well as a non-social control condition (Causal Inference). Across multiple analyses, we found converging evidence of a double dissociation between patients with right superior parietal damage, selectively impaired in Intention Attribution, and those with right antero-medial temporal lesion, exhibiting deficits only in Emotion attribution. Instead, patients with damage to the frontal cortex were impaired in all kinds of inferential processes, including those from the non-social control conditions. Overall, our data provides novel reliable causal evidence of segregation between different aspects of the ToM network from both the cognitive and also the anatomical point of view.

Temporal prediction can help to follow a trajectory. In case of an error, the prediction can be adjusted. However, processing the error and adjusting the prediction can take time. What happens immediately after a prediction error, and can the processing of the prediction be modulated? We use a newly found illusion based on moving squares and requiring trajectory regularity to be elicited. We examined the conscious consequences of a sub-threshold manipulation of the square trajectories, and transcranial magnetic stimulation (TMS) on the cerebellum (right CRUS I/II) to study the modulation of the processing of the trajectory manipulations. The TMS was a typical intermittent theta-burst stimulation, but only one sequence of around 3 minutes, compared with a placebo stimulation. The trajectory manipulation had a reliable effect on the illusion, even though the illusion emerged within less than 100 ms after the trajectory manipulation. The results suggest that the prediction is temporarily stopped after the trajectory change. The illusion was accompanied by EEG signals whose amplitude was modulated by TMS on the cerebellum, at least in those participants who received verum TMS after having performed the task three times. Those EEG signals resembled a late LPP (Late Positive Potential). As LPP spontaneously decreased over time, the results suggest the effect of TMS may represent a reinstation of the EEG consequences of the prediction error, i.e., a modulation of its significance.

Meta-analysis shows that sub-clusters defined by affected domains of psychosocial functioning capture PTSD subtypes better than symptom clusters defined in the DSM-IV. This pilot study investigated the association between symptom sub-clusters and brain volume in twelve persons with PTSD (females, mean age 40.9 years). Structural magnetic resonance imaging (MRI) images were acquired, and voxel-based morphometry (VBM) was used to estimate local gray matter volume throughout the brain. Participants gray matter volume was correlated with both overall PTSD severity and sub-cluster severities. In this preliminary study examining sub-clusters and brain morphometry, we found that neuronal changes associated with sub-clusters may provide a more complete understanding of the neuroanatomical changes that occur in PTSD beyond what can be ascertained using overall disorder severity or comparisons with control subjects. The results of our study suggest that the neurobiological changes resulting from severe trauma depend on the specific sub-clusters of symptoms experienced by individuals with PTSD.

Humans complete different types of sequences as a part of everyday life. These sequences can be divided into two important categories: those that are abstract, in which the steps unfold according to a rule at super-second to minute time scale, and those that are motor, defined solely by individual movements and their order which unfold at the sub-second to second timescale. For example, the sequence of making spaghetti consists of abstract tasks (preparing the sauce and cooking the noodles) and nested motor actions (stir pasta water). Previous work shows neural activity increases (ramps) in the rostrolateral prefrontal (RLPFC) during abstract sequence execution (Desrochers et al., 2015, 2019). During motor sequence production, activity occurs in regions of the prefrontal cortex (Yewbrey et al., 2023). However, it remains unknown if ramping is a signature of motor sequence production as well or solely an attribute of abstract sequence monitoring and execution. We tested the hypothesis that significant ramping activity occurs during motor sequence production in the RLPFC. Contrary to our hypothesis, we did not observe significant ramping activity in the RLPFC during motor sequence production, but we found significant ramping activity in bilateral inferior parietal cortex, in regions distinct from those observed during an abstract sequence task. Our results suggest different prefrontal-parietal circuitry may underlie abstract versus motor sequence execution.

Early life stress (ELS) in primates alters dopamine function, contributing to addiction, hyperactivity, cognitive deficits, aggression, and social subordinance. To assess whether dopamine receptor densities are affected by ELS, male juvenile rhesus monkeys (Macaca mulatta) were either mother-reared (MR, N=6) in a semi-natural environment or nursery-reared (NR, N=6) with peers in a laboratory. At 1 [1/2] years of age, subjects were sacrificed and the left prefrontal cortex (PFC), striatum (caudate and putamen), nucleus accumbens (NAcc), and claustrum (CLA) were explored through quantitative autoradiographic studies of dopamine receptor-1 (DRD1) and -2 (DRD2) conducted using [125I]-(+)-SCH 23982 and 125I-Epidepride, which have high affinity and selectivity for DRD1 and DRD2, respectively. No group differences emerged in striatal or NAcc receptor binding. However, MR monkeys exhibited significantly greater DRD1 binding in the left orbital PFC and significantly greater DRD2 binding in both the left medial PFC and right CLA compared to NR. These findings implicate the medial PFC (stress vulnerability, cognition), orbital PFC (reward valuation), and CLA (anxiety modulation) as critical sites disrupted by maternal deprivation. Therefore, we propose that nursery-rearing induces a hypodopaminergic prefrontal-claustral ecophenotype, underlying the cognitive, affective, and social impairments observed in NR monkeys.

the crown of the human Superior Frontal Gyrus (SFG-crown) is a functionally independent region, nestled between the dorsal premotor and supplementary motor cortices, that supports internally-timed action control. The unique SFG-crowns connectivity fingerprint by the Frontal Aslant Tract (FAT), suggests a caudal-rostral pattern of increasing abstractness of action representations. Coherently, since the mid-portion of the caudal SFG contains a representation of action strategies that involve internal timing, we hypothesized that the caudal portion of the SFG may be involved in action execution of internally-timed actions. To test this, we asked 21 healthy participants to perform a self-paced tapping movement with the right index finger or a self-paced articulation of the syllable /da/ while applying online single-pulse TMS to the posterior, middle and anterior origins of the FAT in the left SFG-crown. Results showed that effective TMS (compared to sham) impacted rhythm production in both tasks, only when applied to the posterior SFG region, by reducing the probability of motor events in the 200 ms following TMS. The present data support the hypothesis, that the posterior SFG-crown, associated with the most posterior origin of the FAT fibers, is involved in the production of internally-timed actions, in an effector-independent modality, suggesting a domain-general role in the execution of internally-timed movements.

Cortical and subcortical lesions to the motor system, as often occur with stroke, typically lead to transitions through a stereotyped upper limb recovery sequence. After initial weakness and loss of dexterity, spasticity and fixed muscle coactivation patterns (synergies) appear. Early work suggested that different features arise from distinct primary motor cortex (M1) subdivisions. Here we investigated this with modern methods, using ischemic lesions of various cortical areas and electrocoagulation lesions of magnocellular red nucleus (RNm) in rhesus monkeys. Nine animals were trained on a reach and grasp task; hand kinematics were assessed with markerless tracking. The proportion of damaged cortical layer V cells in each cortical area was quantified, and corresponding kinematic effects evaluated. Reaching speed showed greater and more persistent reductions with larger lesions to the posterior part of M1 on the gyrus (Posterior Old M1 in Strick's terminology). Initial increases in trajectory variability were more consistent with greater damage within the central sulcus (New M1); these partially recovered. Lesions involving Anterior Old M1 (Area 4s in Hines' terminology) had no additive negative effects. An extensive cortical lesion, which combined New and Old M1 with pre-motor and somatosensory cortex damage did not produce a worse or more persistent deficit than lesions limited to M1, suggesting that loss of arm control arose mainly from damage to descending pathways rather than cortico-cortical interactions. Lesions of RNm led to long-lasting slowing of reach, but no increase in variability. Subsequent cortical lesions to Old M1 led to more severe effects, and worse recovery, than without the preceding RNm lesion. This suggests an important neural compensatory role for the rubrospinal tract following cortical damage in monkey, which is not available in humans where the rubrospinal tract is vestigial. None of the lesions investigated led to overt abnormal synergies. The results are consistent with known differences in descending connections from each area: New M1 has fast cortico-motoneuronal output, known to be important for fine motor control (here assessed by trajectory variability); Old M1 has cortico-reticular connections able to activate the reticulospinal tract, important for generating the high forces needed for fast movements.

ObjectivePatients with refractory epilepsy experience extensive and invasive clinical testing for seizure onset zones treatable by surgical resection. However, surgical resection can fail to provide therapeutic benefit, and patients with neocortical epilepsy have the poorest therapeutic outcomes. This case series studied patients with neocortical epilepsy who were referred for surgical treatment. Prior to surgery, patients volunteered for resting-state functional magnetic resonance imaging (rs-fMRI) in addition to imaging for the clinical standard of care. This work examined the variability of functional connectivity in patients, estimated from rs-fMRI, for associations with surgical outcomes. MethodsThis work examined pre-operative structural imaging, pre-operative rs-fMRI, and post-operative structural imaging from seven epilepsy patients. Review of the clinical record provided Engel classifications for surgical outcomes. A novel method assessed pre-operative rs-fMRI from patients using comparative rs-fMRI from a large cohort of healthy control subjects and estimated Gibbs distributions for functional connectivity in patients compared to healthy controls. ResultsThree patients had Engel classification Ia, one patient had Engel classification IIa, and three patients had Engel classification IV. Metrics for variability of functional connectivity, including absolute differences of the functional connectivity of each patient from healthy control averages and probabilistic scores for absolute differences, were higher for patients classified as Engel IV, for whom epilepsy surgery provided no meaningful improvement. SignificanceThis work continues on-going efforts to use rs-fMRI to characterize abnormal functional connectivity in the brain. Preliminary evidence indicates that the topography of variant functional connectivity in epilepsy patients may be clinically relevant for identifying patients unlikely to have favorable outcomes after epilepsy surgery. Widespread topographic variations of functional connectivity also support the hypothesis that epilepsy is a disease of brain resting-state networks.

Two main types of musical creativity in the western canon are improvisation and interpretation. With improvisation, the fundamental structure of the melody, chords, rhythm and tempo of a piece can be modified, while with interpretation, the focus is on the emotional dynamics. Here we characterise electrical brain activity from professional jazz and classical pianists, whilst they were engaged in these different creative tasks with musical excerpts from both genres. Multivariate EEG was recorded during two phases of each task, mental planning and actual performance. Subsequently neuronal activity patterns were source localised with standardised low resolution electromagnetic tomography (sLORETA). For each musical performance, we obtained both subjective (self-rated) and objective (blind, expert-rated) measures of musical creativity. Across both tasks and genre backgrounds, within the first and middle 4 second segments of the performance phase, for musical performances that were judged highly creative objectively by external expert music assessors, we observed an increased activation in the anterior cingulate and medial prefrontal cortex (Brodmann area, BA32), suggesting a maintenance of executive control, and integrating motoric and emotional communication during creativity. Across genre backgrounds, within the performance phase for the interpretation task compared to the improvisation task, there was an increased activity in the insula (BA 13), suggesting a convergent creative task from the linked goal-orientated conscious error-monitoring and audio-visual integration functions. Genre profession also gave rise to differences across phases; jazz pianists presented a decreased parietal (BA7) activity during improvisation tasks suggesting a role for defocussed attention and for classical pianists, both tasks were associated with occipitotemporal (BA 37) activity which is involved in semantic/ metaphorical processing suggesting a close adherence to the visual score. These 3 areas relate the cognitive demands of the creative musical task to the demands of the corresponding genre of music. HighlightsO_LIEEG activity associated to musical creativity types: Improvisation and Interpretation C_LIO_LIIncreased activity in Insula (BA 13) for Interpretation suggest convergent creativity C_LIO_LIDecreased Precuneus (BA7) activity for Improvisation suggest defocussed attention C_LIO_LIIncreased activity in medial prefrontal cortex (BA32) in highly creative performance C_LI

Neuroscientific research has shown that perceptual decision-making occurs in effector-specific brain regions that are associated with the required motor response. Recent functional magnetic resonance imaging (fMRI) studies that dissociated decisions from coinciding processes, such as motor actions partly challenge this, indicating abstract representations that might vary across stimulus modalities. However, cross-modal comparisons have been difficult since most task designs differ not only in modality but also in effectors, motor response, and level of abstraction. Here, we describe an fMRI experiment where participants compared frequencies of two sequentially presented visual flicker stimuli in a delayed match-to-comparison task, which controlled for motor actions and stimulus sequence. Using Bayesian modelling, we estimated subjective frequency differences based on the time order effect. These values were applied in support vector regression analysis of a multi-voxel pattern whole-brain searchlight approach to identify brain regions containing information on subjective decision values. Furthermore, a conjunction analysis with data from a re-analyzed analogue vibrotactile study was conducted for a cross-modal comparison. Both analyses revealed significant activation patterns in the left dorsal (PMd) and ventral (PMv) premotor cortex as well as in the bilateral intraparietal sulcus (IPS). While previous primate and human imaging research have implicated these regions in transforming sensory information into action, our findings indicate that the IPS processes abstract decision signals while PMd and PMv represent an effector-specific, but motor response independent encoding of perceptual decisions that persists across sensory domains.

The reward positivity (RewP) is an event-related brain potential (ERP) component associated with feedback and reward processing. Although the component is said to be generated in anterior cingulate cortex (ACC), this inference is disputed because of the inverse problem. Recently, by conducting a current source density analysis of intracranial electroencephalogram (EEG) data recorded from a large cohort of epilepsy patients, we provided direct evidence that the RewP is produced by a circumscribed region in caudal ACC corresponding to Brodmann areas 24c and 32. In the present study we confirm that this brain area is the source of the RewP by examining the effects of damage to frontal cortex on RewP amplitude. We recorded scalp EEG from 68 stroke patients with damage to frontal cortex while they engaged in a trial-and-error guessing task used to elicit a canonical RewP. Application of non-parametric voxel-based lesion-symptom mapping to the lesion data revealed that damage to Brodmann areas 24c and 32 attenuated RewP amplitude, whereas damage to other parts of frontal cortex did not affect it. These results provide causal evidence that the caudal ACC generates the RewP and underscore the contribution of this brain region toward motivating extended behaviours. Significance statementThe reward positivity (RewP) is an event-related brain potential component that reflects reward processing in the brain. Although multiple studies have suggested that anterior cingulate cortex (ACC) is the neural generator of the RewP, this assertion is disputed mainly because of the inverse problem. In this study, we present direct evidence that the RewP is generated in caudal ACC by performing voxel-based lesion-symptom mapping (VLSM) in a cohort of 68 stroke patients with lesions in the frontal lobe. We found that a circumscribed region in right caudal ACC was significantly associated with a reduced RewP, providing the first causal evidence that this region generates the RewP in humans. These fundings elucidate the central role ACC plays in motivating extended behaviours.

According to dual-process theories, recognition memory draws upon both familiarity and recollection. It remains unclear how primate prefrontal cortex (PFC) contributes to familiarity and recollection processes but frequency-specific neuronal activities are considered to play a key role. Here, non-human primate (NHP) electrophysiological local field potential (LFP) recordings first showed that a specific subregion of macaque PFC (i.e., dorsolateral PFC, dlPFC) was implicated in task performance at a specific frequency (i.e., increased beta power in the 10-15 Hz range observed in correct versus error trials) in a specific phase of a recognition memory task (i.e., during sample presentation). Then, to assess generalization to humans and causality we targeted left human dlPFC (BA 9/46) as well as left dorsomedial prefrontal cortex (BA 8/9) for comparison, and also vertex as a control, with transcranial magnetic stimulation at a frequency in the middle of the low-beta range observed in NHP (i.e. 12.5 Hz) and compared that to non-frequency-specific stimulation, and also to a no-stimulation control, during occasional sample presentations within a similar task. Hence we investigated hypotheses about the causal importance for human memory of a location-specific, frequency-specific, and task-epoch-specific intervention derived directly from the NHP electrophysiological observations. Using a dual-process signal detection (DPSD) model based on analysing receiver operating characteristics (ROC) curves, we showed beta-frequency TMS caused decreased recollection when targeted to human dlPFC, but enhanced familiarity when targeted to dorsomedial prefrontal cortex. Non-frequency-specific patterns of stimulation to all sites, and beta-frequency stimulation to vertex, were all without behavioural effect. This study provides causal evidence that PFC-mediated contributions to object recognition memory are modulated by beta-frequency activity; more broadly it provides translational evidence bridging NHPs and humans by emphasizing functional roles of beta-frequency activity in homologous brain regions in recognition memory. HighlightsO_LIlow beta power in NHP dlPFC during stimulus encoding was related to behaviour C_LIO_LIhuman rTMS study used parameters derived from NHP observations to test causality C_LIO_LIlow beta rTMS to human dlPFC, but not dmPFC, impairs recollection C_LIO_LIlow beta rTMS to human dmPFC, but not dlPFC, enhances familiarity C_LIO_LIprovides cross-species validation of prefrontal beta power to primate recognition C_LI